IAP Antagonists Induce Autoubiquitination of c-IAPs, NF-κB Activation, and TNFα-Dependent Apoptosis
نویسندگان
چکیده
Eugene Varfolomeev,1 John W. Blankenship,1 Sarah M. Wayson,1 Anna V. Fedorova,1 Nobuhiko Kayagaki,2 Parie Garg,2 Kerry Zobel,1 Jasmin N. Dynek,1 Linda O. Elliott,3 Heidi J.A. Wallweber,1 John A. Flygare,3 Wayne J. Fairbrother,1 Kurt Deshayes,1 Vishva M. Dixit,2,* and Domagoj Vucic1,* 1Department of Protein Engineering 2Department of Physiological Chemistry 3Department of Medicinal Chemistry Genentech, Inc., South San Francisco, CA 94080, USA *Correspondence: [email protected] (D.V.), [email protected] (V.M.D.) DOI 10.1016/j.cell.2007.10.030
منابع مشابه
IAP inhibitors enhance co-stimulation to promote tumor immunity
The inhibitor of apoptosis proteins (IAPs) have recently been shown to modulate nuclear factor κB (NF-κB) signaling downstream of tumor necrosis factor (TNF) family receptors, positioning them as essential survival factors in several cancer cell lines, as indicated by the cytotoxic activity of several novel small molecule IAP antagonists. In addition to roles in cancer, increasing evidence sugg...
متن کاملSmac Mimetics and TNFα: A Dangerous Liaison?
Inhibitor of apoptosis proteins (IAPs) such as XIAP, cIAP1, and cIAP2 are upregulated in many cancer cells. It has been thought that small-molecule mimetics of Smac, an endogenous IAP antagonist, might potentiate apoptosis in cancer cells by promoting caspase activation. However, three recent papers, two in Cell (Vince et al., 2007; Varfolomeev et al., 2007) and one in Cancer Cell (Petersen et ...
متن کاملBirinapant (TL32711), a bivalent SMAC mimetic, targets TRAF2-associated cIAPs, abrogates TNF-induced NF-κB activation, and is active in patient-derived xenograft models.
The acquisition of apoptosis resistance is a fundamental event in cancer development. Among the mechanisms used by cancer cells to evade apoptosis is the dysregulation of inhibitor of apoptosis (IAP) proteins. The activity of the IAPs is regulated by endogenous IAP antagonists such as SMAC (also termed DIABLO). Antagonism of IAP proteins by SMAC occurs via binding of the N-terminal tetrapeptide...
متن کاملInhibitor of apoptosis proteins as novel targets in inflammatory processes.
OBJECTIVE Inhibitor of apoptosis proteins (IAPs), such as X-linked or cellular IAP 1/2 (XIAP, cIAP1/2), are important regulators of apoptosis. IAP antagonists are currently under clinical investigation as anticancer agents. Interestingly, IAPs participate in the inflammation-associated TNF receptor signaling complex and regulate NFκB signaling. This raises the question about the role of IAPs in...
متن کاملc-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling.
Ubiquitin ligases are critical components of the ubiquitination process that determine substrate specificity and, in collaboration with E2 ubiquitin-conjugating enzymes, regulate the nature of polyubiquitin chains assembled on their substrates. Cellular inhibitor of apoptosis (c-IAP1 and c-IAP2) proteins are recruited to TNFR1-associated signalling complexes where they regulate receptor-stimula...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Cell
دوره 131 شماره
صفحات -
تاریخ انتشار 2007